Rheumatoid Arthritis in Asians

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Maurice Cummings
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NO DISCLOSURES Rheumatoid rthritis in sians Mary C.

joints Inflammatory Characteristic pattern, symmetric

1 NO DISCLOSURES Rheumatoid rthritis in sians Mary C. Nakamura M.D. Professor of Medicine, UCSF Rheumatoid rthritis Rheumatoid rthritis Polyarthritis of synovial lined joints Inflammatory Characteristic pattern, symmetric Cartilage degradation, erosion of juxtaarticular bone, and joint deformities Systemic, utoimmune disease Prevalence 1% 1

2 R: articular symptoms Inflammatory vs Degenerative rthritis R is an inflammatory arthritis: Swelling, effusion, warmth, erythema Morning stiffness Often lasts hours Can be the dominant symptom Joint pain and stiffness improve with activity gel phenomenon Stiffness recurs after prolonged inactivity R Pain after rest am Stiffness >30 min Soft tissue swelling variable course with flares Specific joint pattern not related to weight bearing Systemic illness O Pain with use Stiffness <30 min Bony hypertrophy Progressive course with chronic sx Weight bearing joints Systemically well Inflammatory vs Degenerative rthritis R WRISTS MCPs PIPs NOT DIPs Systemic illness O NOT WRISTS NOT MCPs PIPs DIPs Systemically well Treat to Target Genetics and R Ethnicity and Treatment Response Comorbidities Osteoporosis Cardiovascular Disease R Treatment and Hepatitis B 2

Early R Treat to Target Current recommended approach to R treatment Setting specific goals to achieve remission or low disease state, rapid escalation of treatment randomized controlled clinical

3 Early R Treat to Target Current recommended approach to R treatment Setting specific goals to achieve remission or low disease state, rapid escalation of treatment randomized controlled clinical trials demonstrated that a TTT strategy can achieve superior clinical outcomes compared with usual care Potential Benefits Decreased long term joint damage Decreased symptoms? Decreased comorbidities Rev in Soloman rth Rheum :775 Treat to Target Barriers Non rheumatologists not as comfortable with R medications particularly biologics ccess to rheumatologist often not rapid Not all rheumatologist measure disease activity Medication side effects Costs of medications Patient preferences R: general features Female:male ratio of 3:1 Peak onset (but can develop at any age) 4 th or 5 th decades (women) 6 th to 8 th decades (men) Genetic Predisposition HL Class II shared epitope Environmental Risk Smoking 3

R: genetic susceptibility Twin studies Concordance: monozygotic > dizygotic twins Concordance for monozygotic twins: 15 30% Heritability 60% Multiple genes involved HL 35% of overall genetic risk HL

4 R: genetic susceptibility Twin studies Concordance: monozygotic > dizygotic twins Concordance for monozygotic twins: 15 30% Heritability 60% Multiple genes involved HL 35% of overall genetic risk HL DRB1 alleles (DR4) Relative risk for R: 4 to 5 fold Mechanism of risk uncertain HL Manhattan plot from a GWS study of R Criswell Immunological Reviews 233: 55, 2010 The Shared Epitope (DRB1*0401) Shared Epitope Hypothesis HL DRB1 alleles and R 74 Q70 73 R72 confers susceptibility to R increases likelihood of CCP+ R amino acid position on the DR chain DRB1 allele Q R R 0401 Q K R 0404 Q R R 0405 Q R R 0408 Q R R 1402 Q R R 1001 R R R CONSENSUS Q/R R/K R 4

HL shared epitope + smoking increases risk for R (anti-ccp+) Global prevalence rates of rheumatoid arthritis (R) Relative Risk EVER SMOKING 0 111 2 Copies of HL shared epitope NO SMOKING

DMRDs 1993 2001 2 main ethnic groups N European and S sian S sian patients more likely to terminate DMRD therapy.

5 HL shared epitope + smoking increases risk for R (anti-ccp+) Global prevalence rates of rheumatoid arthritis (R) Relative Risk EVER SMOKING Copies of HL shared epitope NO SMOKING Klareskog rth Rheum 2006 Genetic Heterogeneity between sian and European patients with R Ethnicity and Treatment Response Not well examined Study in UK retrospective look at R pt receiving DMRDs main ethnic groups N European and S sian S sian patients more likely to terminate DMRD therapy. More common rash/lack of effect/concern re side effects Less GI and respiratory adverse events? Communication?cultural differences?genetic polymorphisms in drug metabolism More studies needed to understand cultural and genetic differences Helliwell Rheumatology :1197 5

6 R Co morbidities Osteoporosis Increased risk in small sian females Increased risk with R / prednisone Often Low calcium diet in sians sians have lower hip fracture than Caucasians but similar vertebral fracture rates in general R patients had a 2.2 fold increased risk of fractures as compared with general population In sian R patients, advanced age and history of prior fracture were the most important risk factors for new fractures Increased Risk with high CCP ntibody titers Kim Rheum Int :1205 Xue Medicine : e6983 R Co morbidities Cardiovascular Disease Increased risk with R active disease or long standing Comparable to that of Type II DM as risk factor Higher CV morbidity and mortality CD and CHF Risk decreased with adequate treatment with methotrexate or biologics Study of 571 R pts in Japan 11% Cardiovascular events : cardiac death, CS, symptomatic CV, or CHF Nurmohamed utoimmun Rev : 663 Gabriel Curr Opin Rheum :171 R Treatments and Hepatitis B sian mericans and Pacific Islanders (PIs) account for more than 50% of nearly one million mericans living with chronic hepatitis B Nearly 70% of sian mericans are foreign born and estimates have found that approximately 58% of foreign born people with chronic hepatitis B are from sia Immunosuppressive therapy carries risks of worsening chronic active disease and reactivating virus in those with latent disease Hepatitis B and R Retrospective Case Control Study in China, 32 with Chronic active Hep B, 128 age/sex/baseline disease activity matched Higher percentage of pt with radiographic progression Higher percentage of pt with active disease f HBV reactivation in 34% (most not on prophylaxis) Chen rth Research and Therapy :81 6

ll R patients should be tested for Hep B status Testing should include HBsb HBsg HBcb Rituximab for R Depletes peripheral B cells for > 6 months R patients can be vaccinated against HBV, considered

7 ll R patients should be tested for Hep B status Testing should include HBsb HBsg HBcb Rituximab for R Depletes peripheral B cells for > 6 months R patients can be vaccinated against HBV, considered safe and produces antibodies in 68% CNNOT Vaccinate pts that are receiving Rituximab Elkayam nn Rheum Dis :623 N Engl J Med 350: 2572, 2004 No ntibody Response to Immunization following Rituximab until B cells return Pescovitz et al J llergy Clin Immunol 128:1295, 2011 R patients receiving immunosuppressive treatment Highest Risk Pt +HBVDN >2000IU or HBeg + (>10% risk reactivation) HBsg+ / HBcb+ / HBsb neg or HBsb / HBcb+/ HBsb neg Need antiviral therapy prior to or concurrently with immunosuppression Lamivudine, entecavir only agents studied though tenofovir has been used in reports Moderate Risk Pt no detectable HBV DN (1 10% risk reactivation) HBsg neg /HBcb+/HBsb Follow HBV DN levels q2 3 months Seetharam Curr Hepatol Rep :235 7

8 R patients receiving immunosuppressive treatment antiviral treatment should generally be continued for six months after immunosuppressive drug therapy is discontinued ntiviral treatment should be continued for 12 months when rituximab is used or whenever HBV DN above 2000 IU or 10,000 copies/ml is observed at baseline Vaccinations for R patients Yearly Flu vaccine Pneumococcal PCV 13 (prevnar conjugate) vaccination once. Pneumococcal PPSV 23 (pneumovax polysaccharide) and revaccination 5 years later. For persons 65 yo, consider the high dose formulation of influenza vaccine which might be more effective. PCV13 vaccination should not be performed if the patient has received PPSV23 vaccination within the prior 12 months. PPSV23 vaccination should not be performed if the patient has received PCV13 within the past 8 weeks. Patients who received PPSV23 before age 65 should receive another dose of the vaccine at age 65 or later if at least 5 years have elapsed since their previous PPSV23 dose. Hepatitis B Shingrix (new Shingles vaccine) R in sian Populations General guidelines favor more aggressive treatment to remission Refer early to rheumatologists dvance therapy with shared decision making Vaccinations for immunocompromised patients R in sian Populations Hepatitis B screening prior to immunosuppression Follow HBV DN in HBcb pos/hbsb neg patient anti viral prophylaxis for high risk patients Genetic associations differ in sian populations May have implications in drug response Comorbidities can be significant Osteoporosis Screening for all limit steroids Cardiovascular Risk ssessments Treat other risk factors 8

9 Thanks!! Russell/Engleman Rheumatology Research Center UCSF/SFGH R Cohort Patients, Physicians and Coordinators 9

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